Cyclin D1, an important cell cycle regulator, is overexpressed in several human
cancers including breast. Both
estrogens and
progestins activate the transcription of the gene;
antiestrogens have been shown to reduce
cyclin D1 protein levels.
Cyclin D1 protein overexpression has been strongly associated with well-differentiated,
estrogen receptor-positive
tumors. Little is known, however, as to whether epidemiological risk factors are related to this molecularly defined subset of
tumors. Using a population-based study of young women <45 years in New Jersey, we analyzed whether
oral contraceptives (OCs) and other risk factors were associated with the overexpression of
cyclin D1 in
breast cancer tissue. We measured
cyclin D1 status in
paraffin-embedded, archived tissue from 78.8% of the
breast cancer cases using immunohistochemistry.
Cyclin D1 was overexpressed in 33.7% of the cases (123 of 365). We used unordered polytomous logistic regression to estimate the odds ratios (
ORs) for two case groups--(a)
breast cancer with
cyclin D1 overexpression (n = 123) and (b)
breast cancer without overexpression (n = 242)--compared with 462 population-based controls. The multivariate-adjusted OR for ever use of OCs was 1.6 [95% confidence interval (CI), 1.0-2.5] for cases that overexpressed
cyclin D1 and 1.0 (95% CI, 0.7-1.5) for those with no overexpression. Among women who started using OCs at least 20 years before the reference date, the OR was increased 2-fold for
breast cancer with
cyclin D1 overexpression (OR, 2.2; 95% CI, 1.2-4.0) but not for
breast cancer without
cyclin D1 overexpression (OR, 1.1; 95% CI, 0.7-1.8). If replicated, these findings suggest that early OC use may be associated with the subset of mammary
tumors that overexpress
cyclin D1.